(De)carboxylation reactions incur a high kinetic barrier due to the build-up of negative charge on the atom α to the carboxylate group. Nature has overcome this by employing cofactors such as thiamine pyrophosphate, pyridoxal phosphate and metal ions that can act as electron sinks. Prenylated flavin mononucleotide (prFMN) is the most recently discovered decarboxylation cofactor and it is utilized by the UbiD family of enzymes for catalysing (de)carboxylations on a variety of substrates. Studies on the UbiD enzyme, ferulic acid decarboxylase, provide evidence for the formation of an unprecedented 1,3–dipolar cycloaddition adduct between the substrate and prFMN as a key step in the mechanism. Recently, a new UbiD enzyme, PhdA, was discovered that catalyzes the decarboxylation of phenazine-1-carboxylic acid (PCA) to phenazine. Phenazines are redox-active metabolite produced by <i>Pseudomonas</i> spp. that play a key role in biofilm formation and antibiotic activity. Here we present studies on the substrate scope and mechanism of PhdA. We show that the enzyme catalyzes decarboxylation of a number of aromatic acids, including anthracene-1-carboxylic acid (AnCA). These results have potential biocatalytic applications, especially if conditions can be established under which the carboxylation of aromatic hydrocarbons by PhdA becomes feasible.

Enzymatic decarboxylation of aromatic substrates – a novel role for flavins

ACS Fall 2021

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